Molecular Anatomical Pathology

The Molecular Anatomic Division was established in the early 1990s and provides a unified NATA accredited Molecular Diagnostic Service for all public and regional hospitals and several private laboratories in Perth.  

The Molecular Pathology section provides patients and clinicians specialised DNA and RNA-based testing of tumours for purposes of accurate diagnosis, prognostication and prediction of response to tumour-specific therapies. Diagnostic modalities include the use of PCR, RT-PCR, digital PCR, capillary electrophoresis, pyrosequencing, multiplex-ligation dependent probe amplification (MLPA) including methylation specific MLPA, microsatellite instability (MSI), T- and B-cell gene rearrangements, Array Comparative Genomic Hybridisation, massively parallel sequencing and comprehensive genomic profiling.

In lymphomas the tests are used to establish cell lineage and B-cell or T-cell clonality, essential for accurate classification and treatment. Somatic mutation testing for a number of non-inherited cancers, such as EGFR testing for non-small cell lung cancer, are performed to determine response to tyrosine kinase inhibitor therapy. Similar testing for other genes is performed in the setting of metastatic malignant melanoma (BRAF and C-KIT mutations), gastrointestinal stromal tumours (C-KIT, PDGFRα) and colorectal cancers (KRAS and BRAF mutations), results of which impact on the choice of therapy. Testing for microsatellite instability in colorectal carcinomas is also performed to identify patients who may have hereditary non-polyposis colorectal carcinoma (Lynch Syndrome), which has implications for further genetic testing in families. In addition, methylation specific MLPA is used to further exclude Lynch Syndrome in colorectal and endometrial carcinomas.

The laboratory performs PCR-based chromosome translocation assays for accurate subtyping of lymphomas and diagnosis of sarcomas as deemed necessary by the lymphoma pathologist.  Array Comparative Genomic Hybridisation is used as an ancillary test for refining the diagnosis of morphologically ambiguous metastatic lesions.   MLPA is used for the prognostic stratification of uveal melanomas. Latest technology is in digital PCR, a highly sensitive and specific assay that can be used to detect variants that are present at very low levels, including in low amounts of DNA, for example circulating cell-free DNA extracted from blood samples are utilised. This assay is used to detect the EGFR T790M variant that confers resistance  to tyrosine kinase inhibitors in lung cancers; the MYD88 p.L265P variant for diagnosis of Lymphoplasmacytic Lymphoma and the C-KIT p.D816V variant which is used for diagnosis of mastocytosis.

The laboratory runs a number of massively parallel sequencing (MPS, Next Generation Sequencing (NGS)) panels, including a customised 33 gene cancer panel that covers clinically important biomarkers for diagnosis, prognostication and treatment selection for a broad range of common cancer types. This panel is highly suited to the analysis of colorectal, lung, melanoma, ovarian, GIST, glioma and breast cancers as it covers the most common variants in these cancer types. The panel also covers the MYD88 and KIT genes and TERT promoter which is part of the WHO guidelines for diagnostic and prognostic stratification of glioma.

In addition, the laboratory performs comprehensive genomic profiling using large MPS cancer panels which are able to analyse both DNA and RNA, thereby analysing single nucleotide and insertion/deletions variants, copy number variants, gene rearrangements, gene fusions and structural variants. This panel is particularly suitable for patients who have progressive disease, exhausted conventional treatment options, have rare cancer types or for alignment with clinical trials. The TST170 and TSO500 gene panels also analyse microsatellite instability (MSI) status and Tumour Mutation Burden which is predictive for immunotherapies. The Molecular Pathology laboratory has links with Genetic Services of WA, PathWest Discipline of Diagnostic Genomics and the Cytogenetics Laboratory.

 

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Molecular Anatomical Pathology (AP) Community Health Program (CHHP)

Download Community Health and Hospital Program Information

The community Health and Hospital Program funded project entitled ‘Statewide Comprehensive Genomic Testing to Expedite Excellence in Treatment Of Western Australian Cancer Patients’ was commenced 1st July 2020. A total of $19M in funding will be received in Molecular AP over four years to provide an opportunity for comprehensive genomic profiling (CGP) using state of the art Next Generation Sequencing technology for all WA cancer patients.  CGP is providing biomarker information that is used to refine diagnosis, prognosis and align patients with the most suitable treatment strategy according to the profile of their own tumour. This has been particularly beneficial for patients for whom conventional treatment options have been exhausted.  Through this program we have successfully identified biomarkers that have led to new treatment strategies and enrolment in clinical trials. The molecular AP department now analyses a more diverse set of cancers than those routinely received, including rare cancers, such as sarcomas, which have less well understood molecular pathologies.

The project is overseen by an Advisory Committee consisting of eminent health professionals and other key leaders: Medical Oncologists, Prof Michael Millward, Prof Anna Nowak (SCGH), Dr Tom Ferguson (FSH), the Director of Population Health Genomics, Professor Kristin Nowak, clinical Professor Benhur Amanuel (Director of Services, AP, PathWest) and clinical Professor Dominic Spagnolo, Scientist-in-Charge, Molecular AP, Dr Cleo Robinson, Genetic Services Clinical Associate Professor Nick Pachter, Pathwest Chief Finance Officer, Mr Adrian Bautista and a highly experienced community member, Dr Susannah Morris, who provides important insights from the lay and lived-experience perspective.

The project has enabled the discipline to establish streamlined testing pathways across the major teaching hospitals, both public and private and also regional centres. The CHHP project provides support to both local and national programs for Comprehensive Genomic Profiling including Linear Clinical Trials, and has opened an opportunity for collaboration with the Garvan Institute in Sydney for the Molecular Screening and Therapeutics (MoST) program. Through the project we have now developed a rich network with researchers and clinicians across all of WA, including UWA, ECU and Curtin Universities and all of the major cancer treatment centres from both the private and public sectors, with experienced collaborating principal investigators at each site. In addition, we have strengthened our links with local clinical trials institutes such as the Linear Clinical Research for whom we are increasingly the designated testing centre to determine patient eligibility for trials.

Clinicians select and consent patients who would benefit from comprehensive genomic profiling and these referrals go through a rigorous workflow of pre-analytical review for specimen suitability and undergo massively parallel sequencing using the 523 gene panel followed by bioinformatics analysis and clinical interpretation of test results. The Molecular Tumour Board (MTB) meetings are now an established component of the CGP workflow. These meetings are attended by Pathologists, Clinicians and Scientists to discuss the profiling results of each case that has undergone comprehensive testing. At the meeting, which can be attended using a virtual platform, discussion of each case commences with a clinical summary providing the context for the test results in terms of pathological details, ECOG status, previous treatments, patient clinical history and family history of cancer. This enables the attendee clinicians to make a clinical recommendation based on the testing profile that is in the context of the patients’ current clinical situation in order to deliver the best outcome. Due to an increased demand for CGP these meetings are now held weekly.  Thorough the CHHP, as well as local and national collaborations, new treatment options are becoming available to WA cancer patients.

For all sites: Please complete the Clinical Information Form to accompany your referral

 

Download a Patient Informed Consent Form	Download a Patient Informed Consent Form
Sir Charles Gairdner Hospital (NMHS)	St John of God Health Care Subiaco
King Edward Memorial Hospital (NMHS)	St John of God Health Care Murdoch
Perth Children's Hospital (NMHS)	St John of God Health Care Midland
Fiona Stanley Hospital (SMHS)	St John of God Health Care Bunbury
Royal Perth Hospital (EMHS)	Hollywood Private Hospital
WA Country Health Service (WACHS)	Joondalup Health Campus (NMHS)
Icon Cancer Centre - Rockingham and Midland	Peel Health Campus
Rockingham General Hospital	Genesis Care Mandurah Patient Informed Consent Form coming soon

Contact Dr Benhur Amanuel or Dr Cleo Robinson

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Medicare Approved Tests

Primary Site	Diagnosis	Test Description	Medicare Item Number	NATA Accreditation
Colorectal Request form	Stage IV metastatic colorectal cancer	Detection of KRAS exons 2, 3 and 4 (Somatic variant detection)	73338	Fully accredited by NATA
Glial  Neoplasms Request form	Glioma	IDH1 and IDH2 (Somatic variant detection)	73372	Fully accredited by NATA
	Glioma	MGMT promoter methylation	73373	Fully accredited by NATA
	Glioma, glioneuronal tumour or glioblastoma	Detection of the following variants: - IDH1, IDH2  -TERTp - BRAF	73429	Fully accredited by NATA
Gynaecological Malignancies  Request form	Granulosa cell ovarian tumour	FOXL2 c.402C>G (Somatic variant detection)	73377	Fully accredited by NATA
	Advanced (FIGO III-IV), high grade serous or high grade epithelial ovarian, fallopian tube or primary peritoneal cancer	Detection of BRCA1 and BRCA2 variants (Somatic variant detection)	73301	Fully accredited by NATA
	Advanced (FIGO III-IV), high-grade serous or other high-grade ovarian, fallopian tube or primary peritoneal carcinoma	Determination of homologous recombination deficiency (HRD) status, including BRCA1 or BRCA2 status (TSO500-HRD)	73307	Fully accredited by NATA
Lung Request form	New diagnosis of non-squamous non-small cell lung cancer (NSCLC); Single DNA	Single gene detection:  EGFR exon 18, 19, 20, 21 mutation	73337	Fully accredited by NATA
	Locally advanced (Stage IIIb) or metastatic (Stage IV) non-small cell lung cancer (NSCLC); Single DNA	Single gene detection:  EGFR T790M mutation	73351	Fully accredited by NATA
	New diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC);  Single DNA	Single gene detection:  MET hotspot variants, including MET-exon 14 Skipping mutation	73436	Fully accredited by NATA
	New diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC);  Multigene DNA and RNA	Multigene detection:  EGFR, KRAS, BRAF, MET-exon 14, RET, NTRK 1/2/3 fusion status	73437	Fully accredited by NATA
	New diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC);  Multigene DNA only	Multigene detection:  EGFR, BRAF, KRAS and MET-exon 14	73438	Fully accredited by NATA
	New diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC);  Multigene RNA	Multigene detection: ALK, ROS1, RET, NTRK 1/2/3 fusions, in absence of BRAF, KRAS, MET abnormalities	73439	Fully accredited by NATA
Melanocytic Lesions Request form	Stage III or stage IV metastatic cutaneous melanoma	BRAF (Somatic mutation)	73336	Fully accredited by NATA
	Melanocytic lesion diagnosis	Array Comparative Genomic Hybridisation (aCGH)	73287	Fully accredited by NATA
Prostate Request form	Metastatic castration-resistant prostate cancer (mCRPC)	Detection of BRCA1 and BRCA2 variants (somatic mutation)	73303	Fully accredited by NATA
Solid Tumour Request form	Solid tumour (<18 years of age)                          OR Mammary analogue secretory carcinoma of the salivary gland                          OR Secretory breast carcinoma	Detection of neurotrophic receptor tyrosine kinase (NTRK1, NTRK2, NTRK3) fusions	73433	Fully accredited by NATA
	Solid tumour	Detection of gene rearrangements by NGS: - EWSR1 - NTRK 1, NTRK3  - PDGFRB - PAX3 - PAX7 - ALK  Detection of copy number variants (CNV) by NGS: - MDM2	73374	Fully accredited by NATA

 

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Non-Medicare Tests

Primary Site	Diagnosis	Test Description	NATA Accreditation
Gastrointestinal Tract Request form	Gastrointestinal stromal tumours (GIST)	Detection of KIT exon 9, 11, 13, 17 and 18 activating mutations in gastrointestinal stromal tumours (GIST)	Fully accredited by NATA
		Detection of PDGFR alpha exon 12, 14 and 18 activating mutations in gastrointestinal stromal tumours (GIST)	Fully accredited by NATA
Haematological Malignancies Request form	Waldenstrom Macroglobulinaemia (Lymphoplasmacytic Lymphoma (LPL))	Detection of MYD88 p.Leu265Pro (L265P) mutation	Fully accredited by NATA
	Mast cell disease	Detection of KIT p.Asp816Val (D816V) mutation	Fully accredited by NATA
	Leukaemias and lymphomas	Assessment of the clonality status of antigen receptor gene rearrangements in B and T cells	Fully accredited by NATA
Melanocytic Lesions Request form	Uveal Melanoma	MLPA test for uveal melanoma prognosis	Fully accredited by NATA
MSI by Capillary Electrophoresis Request form		Microsatellite Instability test, for microsatellite instability in colorectal carcinomas or any other tumour type	Fully accredited by NATA
Gynaecological Malignancies Request form	Ovarian germ cell tumour	Detection of DICER1 (Somatic variant detection)	Fully accredited by NATA
Solid Tumours Request form		Next Generation Sequencing panel: Ampliseq  Includes analysis of 33 cancer related genes AKT1, ALK, APC, BAP1, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, GNA11, IDH1, IDH2, KIT, KRAS, MAP2K1, MET, MSH6, MYD88, NRAS, PDGFRA, PIK3CA, POLE, PTEN, SMAD4, SRC, STK11, TERTp, TP53	Fully accredited by NATA
		Next Generation Sequencing panel: TST170 Includes analysis of 170 cancer related genes for SNVs and indels, analysis of 59 genes for copy number variation and detection of gene rearrangement (fusions) and splicing events for 55 genes Details available on request	Fully accredited by NATA
		Next Generation Sequencing panel: TSO500 Analysis of 523 cancer related genes for SNVs and indels, analysis of 523 genes for copy number variation and detection of gene rearrangement (fusions) and splicing events for 55 genes. This assay also analyses Tumour Mutation Burden (TMB), Microsatellite Instability (MSI) and Homologous Recombination Deficiency (HRD). Details available on request	Fully accredited by NATA
		Detection of TERT promoter hot spot mutation	Fully accredited by NATA
		Detection of ERBB2 hot spot variants	Fully accredited by NATA
		Detection of GNAQ hot spot variants	Fully accredited by NATA
		Detection of GNA11 hot spot variants	Fully accredited by NATA
		Detection of MAP2K1 hot spot variants	Fully accredited by NATA
		Detection of MET hot spot variants, including exon 14 skipping	Fully accredited by NATA
		Detection of PIK3CA hot spot variants	Fully accredited by NATA
		Detection of POLE hot spot variants	Fully accredited by NATA
		Detection of TP53 loss of function variants	Fully accredited by NATA